Non-invasive glucose measuring device and method for measuring blood glucose

ABSTRACT

A glucose measuring device for determining the concentration of glucose in intravascular blood within a body part of a subject. The device includes at least one light source having a wavelength of 650, 880, 940 or 1300 nm to illuminate the fluid. At least one receptor ( 14 ) associated with the light source ( 12 ) for receiving light and generating a transmission signal representing the light transmitted is also provided. A support piece is including for supporting the light source associated with the respective receptor. The support piece is adapted to engage a body part of a subject. Finally, a signal analyzer determines the glucose concentration in the blood of the subject. A method for determining the glucose concentration is also provided which calibrates a measuring device and sets the operating current for illuminating the light sources during operation of the device. Once a transmission signal is generated by receptors ( 14 ) receiving light via the light source and illuminated blood, and the high and low values from each of the signals are selected and stored in the device ( 20 ), the values are subtracted to obtain a single transmission value for each of the light sources. These calculated values are then compared to a database of target transmission values, either using a neural network, or directly compared to determine the glucose concentration, which value is then displayed ( 28 ) on the device.

Applicant hereby claims priority to PCT application PCT/US97/08852,filed Jun. 5, 1997, and this application is a continuation-in part ofSer. No. 08/803,066 U.S. Pat. No. 5,910,109 filed Feb. 20,1997.

TECHNICAL FIELD

The present invention relates generally to a medical diagnosticmeasurement instrument, and, more specifically, to a device and methodfor obtaining non-invasive quantitative measurements of blood glucose inpatients.

BACKGROUND

The frequent monitoring of blood glucose levels in individuals withdiabetes mellitus has become a major factor in the care of such patientsover the past decade. Currently, it is possible for the diabetes patientand health care professionals to measure and record blood glucose levelsusing a variety of portable devices. Due to the need for multiple dailymeasurements, invasive blood for samples are a burden on the patient andoften expensive. As a result, non-invasive devices using spectroscopictechniques, and which are battery powered and use solid-stateelectronics, have begun to be commercialized. Used at home, thesedevices allow diabetes patients to monitor and respond to fluctuationsin blood glucose on a daily basis.

One example of such a device is disclosed in U.S. Pat. No. 5,070,874 toBarnes, et al. (“the '874 patent”). As set forth in the '874 patent,human blood glucose concentration levels vary greatly, and are foundwithin the range of 0-600 milligrams per deciliter (mg/dl). Normal humanblood glucose levels are in the approximate range of 80-110 mg/dl.Devices of the type disclosed in the '874 patent involve measurement ofblood components using near infrared radiation and spectroscopicabsorption techniques. Additional devices of this type are disclosed inU.S. Pat. Nos. 5,379,764 and 4,882,492, as well as numerous others,which make use of both reflectance and transmission spectroscopicanalysis techniques.

Problems with these prior art devices have resulted due to severalissues. One problem is the overlap of the spectrum of glucose with otherblood sugars and chemicals. Another relates to hemoglobin-glucosebinding, which renders discrete spectral measurements difficult. Also,spectroscopic techniques are typically unable to discriminate betweensugars that are metabolized and those that are excreted, resulting inerroneous readings. Still further, prior art devices have failed toaddress issues which directly impact the accuracy of the measurementstaken, such as the spectral effect produced by the skin and tissue, aswell as variable blood vessel and skin thickness and composition.

As a result of these and other problems, the repeatability and resultingaccuracy of such devices has not been in the range it is desired. TheU.S. Food and Drug Administration is currently advising thatnon-invasive glucose measuring devices should have an accuracy in therange of 15% error or less.

SUMMARY OF THE INVENTION

According to the present invention, a transmission glucose measuringdevice is provided which uses a signal sensor assembly to illuminateintravascular blood or fluid components in the body. The assemblyincludes near infrared light sources on an external surface of atranslucent body to illuminate blood or fluid, and light receptorspositioned on an opposite external surface of the same body, to receiverespective signals representing the radiation transmittance through thetissue and blood or fluid components illuminated. In the preferredembodiment one (1) light source emitting near infrared light ofapproximately 940 nm wavelengths is used. Alternatively, additionallight sources, from two (2) to four (4) light sources, may be usedemitting near infrared and infrared light between preferably 640 and1330 nm, more preferably 650 and 1300 nm wavelengths. A fifth (5)possible light source may also be used, which would repeat one of theprevious four (4) wavelengths. The light sources in the preferredembodiment are light emitting diodes (LEDs) which are pulsed at 1kiloHertz (kHz) for a 1 millisecond (ms) pulse width. Where more thanone receptor, or sensor, is used, each operates at a time when the otherreceptors are off to avoid further noise and signal contamination. TheLEDs and opposite receptors are mounted on a biased or spring biasedsupport for convenient attachment of the LEDs and receptors to the bodypart. In the preferred embodiment, a spring biased support is used formounting on external surfaces of the human ear. The range of pressureapplied to the ear by such supports and the associated LEDs andreceptors should be no more than 15-30 mm of mercury (Hg), and ispreferably much less, for example, 0.4 oz/square inch. It is understoodthat numerous shapes and configurations for the support could be used,depending on the shape of the body or body part to be measured.

Prior to use of the device, upon turning the device on a self-check isperformed to ensure that all LEDs and respective receptors are operatingto specification. Prior to use of the device, a calibration process isconducted to establish settings within the device which consider theskin or tissue and blood flow characteristics of the subject. Suchcalibration is believed to enable improved accuracy and predictabilityin glucose measurement in the present device, since factors such astissue thickness and composition, as well as blood flow, are taken intoconsideration. Intensity calibration involves setting the intensity ofthe LEDs based on an LED intensity factor which is derived from the highand low data values measured from a pulse waveform signal.

The pulse of the subject is measured using an LED and its associatedreceptor to obtain the pulse waveform signal. The high and low bloodflow data values collected to obtain the pulse waveform signal of thesubject are converted and stored in a digital processor, such as an LEDsignal processor. Once the high and low pulse waveform signal values areknown, the blood flow characteristics of the subject are used for theintensity calibration.

The intensity factor may be established based upon initial readings ofthe pulse waveform signal. Current is increasingly supplied to the LEDto increase the intensity of the light source in a stepped fashion atone of multiple increments, until a minimally distorted desirable signalis received by the receptor. Once an acceptable signal is received, thisselected level of LED intensity is stored by the processor, and becomesthe level of current applied to each LED during operation of the device.Additionally, each LED is operated to determine that it is properlyoperational and that its respective receptor is receiving the LED'ssignal at the desired LED intensity. Alternately, the LED intensityfactor may be established using a baseline voltage of approximately 1.2volts. The LEDs are continuously checked by the device to ensure properoperation. In the event no signal is received, the device prevents ameasurement from being taken and issues a warning notice to theoperator.

Still another step in device calibration involves determining from thepulse waveform signal when measurements or readings should be taken bythe device. Measurements of the LED signal are preferably only taken ata midpoint in the blood flow cycle, or at the“baseline” of the pulsewaveform signal. For example, the difference between the high and lowdata values from the pulse waveform signal result in a value which isprovided to the signal processor for establishing the timing ofmeasurements, or signal generation, taken by the device with respect tothe blood flow of the subject. Once the LED intensity factor and thebaseline of the pulse waveform signal are determined, the device theninitiates the operation and measurement of each of the LED signals,preferably through an ear lobe of the subject. Measurements from eachLED are preferably taken several predetermined times, for example 30seconds, at each of the high and low pulsatile values measured over 5milliseconds, with the resulting sensor signal values stored andamplified in a sample and hold amplifier in the LED signal processor,converted in an analog-to-digital (A/D) converter, and normalized andaveraged to obtain a single digital data value for each LED signal.

This pre-processed digital signal value from the LED signal processor isthen provided to a further digital processor, preferably via a personalcomputer interface of the type well known to those of skill in the art.The digital processor is preferably a personal computer supportingconventional software and a database containing predetermined or targetspectral glucose transmittance and absorbance data over a range of 0 to600 mg/dl, for determining the glucose level of the subject from thedigital signal value provided. Alternatively, a trained neural networkcontaining the predetermined or target spectral glucose data may beused. The pre-processed digital signal value is incrementally comparedto target data values in the database or“look-up table” to obtain avalue which is slightly higher than the pre-processed signal value.Alternatively, the database could be used, and the comparison made in atrained neural network which is also well known to one of skill in theart. This closest incremental value, which is calculated by a linearinterpolation between database values if no specific value is locatedwithin the database, is then provided to a digital display as theglucose level for review by the subject.

Other features and advantages the present device will become apparentfrom the following detailed description of the preferred embodiment madewith reference to the accompanying drawings, which form a part of thespecification.

BRIEF DESCRIPTION OF DRAWINGS

In the accompanying drawings, which are incorporated in and constitute apart of this specification, embodiments of the device described areillustrated, and together with the general description above, and thedetailed description below, exemplify the device of the presentinvention.

FIG. 1 is a schematic illustration of a transmission glucose measuringdevice as disclosed;

FIG. 2 is a schematic rear end view of a signal sensor assembly, or thesupport pieces for supporting the light sources and receptors, takenalong the line 2—2 in FIG. 1;

FIG. 3 is a schematic front end view of the support pieces forsupporting the light sources and receptors taken along the line 3—3 inFIG. 1;

FIG. 4 is a schematic cut-away view of the support piece for supportingthe light sources and associated receptors taken along the line 4—4 ofFIG. 3;

FIG. 5 is a high level block diagram of the present device showing asignal sensor assembly, triple output power supply and computer system;

FIG. 6 is a high level block diagram illustrating the major componentsof a signal processing board of the present device;

FIG. 7 is a block diagram of a LED signal processor of the presentdevice;

FIG. 8 is a schematic diagram of LED/sensor blocks LS1-LS4 of thepresent device;

FIG. 9 is a schematic diagram of an LED drive circuit of the presentdevice;

FIG. 10 is a block/schematic diagram of a LED drive and sequencercircuit of the present device; and

FIG. 11 is a schematic side view of an alternate signal sensor assembly,or the support pieces for supporting a light source and receptor;

FIG. 11A is a partial, schematic bottom view of a first support piecefor supporting the light source in the assembly shown in FIG. 11;

FIG. 11B is a partial, schematic top view of a second support piece forsupporting the receptor in the assembly shown in FIG. 11;

FIG. 12 is a schematic bottom view of an insert taken along the line12—12 of FIG. 11, for supporting a light source or receptor;

FIG. 12A is an enlarged schematic, cut-away side view of an insert forsupporting a light source or receptor in the assembly shown in FIG. 11;

FIG. 13 is a schematic side view of another alternate signal sensorassembly, or the support pieces for supporting a light source andreceptor;

FIG. 13A is a schematic top view of the assembly taken along the line13A—13A of FIG. 13; and

FIGS. 14A and 14B are graphic illustrations showing a comparison of theglucose concentration values determined by a prior art invasive bloodglucose meter with the glucose concentration values obtained by thepresent device.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 is a schematic illustration of the non-invasive transmissionglucose measuring device 10 disclosed. The device includes a signalsensor assembly 11 comprising light sources or LEDs 12 and associatedreceptors 14 mounted on an assembly housing 15 comprising opposingspring biased support pieces 16. In the preferred embodiment, eachsupport piece 16 has one or more LEDs 12 and associated receptors 14,for attachment to a body part B of a subject H. The device additionallyincludes a computer system 20 and a power supply 22 as shown in FIG. 5.The computer system 20 comprises a signal processing board 24, signalprocessing logic 26 and a display 28. The computer system components arehoused within a black box or housing 30. The housing has dimensions ofapproximately 4 inches by 8 inches. The display 28 provides the glucoseconcentration measured and calculated by the present device for viewingby the user.

In the preferred embodiment, the signal sensor assembly 11 and itscomponents, as shown in FIGS. 1 to 4, includes the support pieces 16which are adapted for spring biased engagement surrounding portions ofthe human ear B. It is understood that other body parts such as thenose, fingers or toes could also be used. The first support piece 16 asupports and is interconnected with the light sources 12, such that theLED is positioned to illuminate the surface of the ear as illustrated.The second support piece 16 b supports and is interconnected with thereceptors 14 associated with each LED, and are positioned opposite fromtheir respective LEDs for receiving light transmitted from the LEDthrough the ear B.

In one illustrated embodiment, 4 or 5 LEDs emitting near infrared andinfrared light at wavelengths of approximately 650, 880, 940 and 1300nm, with a fifth possible light source used to repeat one of theprevious four wavelengths. In the preferred embodiment a single LED andassociated light source are used, with the LED having a wavelength ofapproximately 940 nm. The LEDs are pulsed at 1 kiloHertz (kHz) for a 1millisecond (ms) pulse width. The LEDs include a housing portion 12 aand a bulb portion 12 b. The conventional LEDs are available fromOptoelectronics of Sunnyvale, Calif. The conventional receptors 14generating the transmission signals through the body part also include ahousing portion 14 a and a sensor portion 14 b. The receptors are alsoavailable from Optoelectronics. Where combinations of LEDs and receptorsare used, each combination of LED and receptor operate at a time whenthe others pair or pairs are off to avoid further noise and signalcontamination. The LED housing 12 a and bulb portion 12 b is more fullyshown in FIG. 4. It should be understood that the receptor housing 14 aand bulb portion 14 b, is identical in its support structure, such thatno further discussion is required. As shown in FIGS. 1 and 4, the firstand second support pieces 16 a, 16 b include an additional support body80 for receiving the LED or receptor housing portions 12 a, 16 a. Thesupport body 80 may be manufactured of any rigid polymer material, suchas Delrin®. The support body 80 includes an opening 82 for receiving theLED or receptor housing portion 12 a, 14 a. At the end of the housingportions 12 a, 14 a, a floating support plate 84 is provided which isengaged with the bulb portion 12 b, 14 b and is movable with respect tothe housing portion 12 a, 14 a. Additionally, an end fitting 86 isprovided which is in press fit engagement with the support body opening82, and includes a bulb opening 87 for receiving the bulb portion 12 b,14 b, of the LEDs and receptors. Intermediate the end fitting 86 and thefloating support plate 84, compression springs 88 are provided. In thisarrangement, the bulb portion 12 a, 14 a of the LEDs and receptors aremovable with respect to the support body 80, such that the bulb portionsare in light spring biased or in floating engagement with the body Bonce they are in communication with the subject H.

As shown in FIGS. 1 and 2, the support pieces 16 a, 16 b, or first andsecond plates which comprise the support piece 16, are interconnected ata pivot point 36 positioned intermediate the support pieces, and includea torsion spring 34 for biasing the support pieces toward one another.Legs 36 a, 36 b are interconnected with the support pieces 16 a, and 16b, respectively, and are engaged through an opening 37 a in the legs byan axle 37 for pivoting motion about the pivot point 36. Thus, thesupport pieces 16 a, 16 b, are manually moved toward one another onfirst ends 38 spaced from the end of the support pieces with the LEDsand receptors 12, 14, to provide a space between the LEDs and receptorsfor the ear, as shown in FIG. 1. Once the assembly 11 is positioned withone of each of the support pieces 16 a, 16 b on either side of the bodypart, the first ends 38 are gradually released to engage the LEDs andreceptors with the body part.

As described here and shown in the preferred embodiment, the signalsensor assembly 11 operates in a manner similar to a spring biasedclothes pin for securing clothing to a clothes line. It is particularlynoted that the spring 34 must have a sufficient force to engage both theLEDs and the receptors with the ear B, but that the spring force is notso great that the intravascular blood flow within the ear is impacted.As previously stated, the force applied should be no greater than 15-30mm of Hg. In the preferred embodiment, the desired pressure or springpressure is approximately 0.4 oz/square inch.

It is also important to note that the arrangement of the support pieces16 a, 16 b, must be such that the LEDs and receptors are at all timesduring operation of the device, aligned or positioned opposite from oneanother to enable proper illumination and receipt of the lighttransmission through the body part B. Thus, it is contemplated that onemay choose to use an alternate arrangement of the spring biased supportpieces, for example, changing the spring 34 position to eliminate thepivot 36, and alternatively provide parallel movement of the each of thesupport pieces, with the axis of the spring transverse to the supportpieces. Further alternate and preferred embodiments of a signal sensorassembly are illustrated in FIGS. 11-13. For ease of understanding,where the elements of the assembly are similar, they are referred tousing the same name, but designated with additional prime designations.Still further it is noted that the spacing between the bulb portions 12b, 14 b, 12 b′, 14 b″, 12 b″, 14 b″ of the LED and receptors ispreferably approximately 3/8 to 3/32 inches. This spacing is believed tomaintain an alignment of within approximately 10° from a center line ofthe bulb portions.

An alternate embodiment of a signal sensor assembly 11′ is illustratedin FIGS. 11-12A. The first support piece 16 a′ and second support piece16 b′ each support an insert 150 for supporting the LED or receptorhousing portions 12 a′, 14 a′. The inserts are press fit into engagementwith the first and second support pieces 16 a′, 16 b′. The insertincludes a bulb opening 87′ where the bulb portions 12 b′, 14 b′ of theLED and receptors project from the inserts 150. Wire channels 152 areprovided for interconnecting the LED and receptor wires 154 with thecomputer system 20. The first and second support pieces 16 a′, 16 b′ areinterconnected at a pivot point 36′, by a pin 156. A torsion spring 34′of approximately 6-8 ounces spring pressure is used surrounding thepivot pin, and engages stop members 158 on an internal surface of eachof the first and second support pieces to maintain the spring 34′ inposition.

In a still further embodiment of a signal sensor assembly 11″illustrated in FIGS. 13-13A, the use of a spring to bias the supportpieces is eliminated. Instead, the first and second support pieces 16a″, 16 b″ are of a somewhat flexible material, such as circuit boardsubstrate, with the LED and receptor housing portions 12 a″, 14 a″mounted by conventional means, such as adhesive, to the material. Rigidspacers 160 are positioned intermediate the first and second supportpieces by conventional fasteners as illustrated. It should be understoodthat use of a sensor assembly of the design of FIG. 13 may not becapable of fitting the body part of all subjects, such that more thanone size of assembly may be required. Additionally, as only theflexibility of the material of the support pieces 16 a″, 16″ maintainsthe assembly 11″ engaged with the ear, an additional support member ispreferably used to maintain the assembly engaged with the ear. Thissupport member, not illustrated, is simply a wire hook arrangementengaged on one end with the assembly 11″, and with a hook end supportedsurrounding the ear of the subject. It is pointed out that thenon-protruding arrangement of the bulb portions 12 b′, 12″, 14 b′, 14 b″of the embodiments of FIGS. 11 and 13 are believed preferable, as thesebulb portions avoid pinching of the ear lobe, which limits blood flow,and thereby increase accuracy of the receptor reading. During repeated,successive tests using the present device, it has been determined thatbest results may be obtained by removing the signal sensor assemblybetween tests and to massage the body part being tested in order toensure that there is sufficient blood flow to the part being tested.Maintaining the assembly 11, 11′, 11″ on the body part between teststends to pinch the body part, somewhat inhibit blood flow, and therebydecrease accuracy.

As shown schematically in FIG. 5, the signal sensor assembly 11 iselectrically interconnected with the computer system 20 to driveillumination of the LED 12, 12′, 12″ and to receive signals from thereceptor 14, 14′, 14″ corresponding to the light transmitted through theear for further processing and display. It should be understood that thepresent device may make use of one or more combinations of LED andreceptor pairs for successful operation. The FIG. 5 high level blockdiagram of the present device shows the signal sensor assembly, tripleoutput power supply and computer system. The triple output power supply22 includes +15 volt, −15 volt and a +5 volt power supply outputs.

As illustrated in FIG. 6 the major components of the signal processingboard 24 include a LED signal processor 40, an analog-to-digitalconverter 42, a signal converter 44, a P/C interface 46 and a controlcircuit 48. Data is transferred between the signal processing board 24and the P/C interface via an I/O bus 49. The P/C interface 46 of thepreferred embodiment is a KB-8 PC-IN-A-Box from KILA of Boulder, Colo.,or a 1×6×3 Compac, Inc. device. It should be understood that numerousconventionally available devices may be used. The illustratedconventional components are in circuit communication with each other asshown in FIG. 6. It should be noted in connection with the conventionalA-to-D converter that additional known techniques are also used toenhance the signal to noise ratio such as the heterodyne detectionscheme. This detection technique is well known to those of skill in theart and eliminates the DC offset problems caused by backgroundillumination. Also, the use of coherent gating are used to improve theoverall measurement accuracy since the measurement of interest isperformed during a period of maximum blood flow. This technique enablesthe dwell time between the blood pulses to be used to obtain ameasurement that yields a DC background value which can be subtractedfrom the peak value. This technique also eliminates measurement problemsassociated with tissue hydration, non-uniform tissue thickness anddensity, as well as patient to patient variation.

Referring now to FIG. 7, a block diagram of the LED signal processor 40of the present device is shown. The LED signal processor 40 includes aLED drive circuit 60 and sequencer circuit 50, an analog switch 52 and aplurality of connections 54 to a plurality of LED/sensor blocks 56 whichare referenced as LS1, LS2, LS3 and LS4. The conventional components arein circuit communication with each other as shown in FIG. 7.

Referring now to FIG. 8, a schematic diagram of LED/sensor blocks 56 orLS1-LS4 of the present device are illustrated. Each LED/sensor block 56includes a LED 12, a sensor 58 and a buffer 59. These well knowncomponents are in circuit communication with each other as shown.

Illustrated in FIG. 9 is a schematic diagram of the LED drive circuit 60of the present device. The LED drive circuit 60 includes a plurality oftransistors (e.g. FET's) 62, drivers (e.g. OCD) 64 and a plurality ofresistors (R, 2R, 4R, 8R and RFET) 66. The LED drive circuit 60 alsoincludes inputs SEL1 through SEL4 68 and an output 69. The conventionalcircuit elements are in circuit communication with each other as shown.

Illustrated in FIG. 10 is a block/schematic diagram of the LED drive 60and sequencer circuit 50 of the present invention. The LED drive andsequencer includes the LED drive circuit 60 of FIG. 5, and a pluralityof transistors (e.g. FET's)70, drivers (e.g. OCD) 71, and a plurality ofresistors (R, 2R, 4R, 8R and R_(FET)) 74. In an alternate design,programmable resistors may be used. The LED drive 60 and sequencercircuit 50 also includes inputs LSEL1 through LSEL4, SEL1 through SEL4,and outputs LED1 DRIVE through LED4 DRIVE. The conventional circuitelements are in circuit communication with each other as shown.

The P/C interface 46 for the signal processing logic 26 may incorporatea conventional trained neural network 27 or, alternately, softwaremaking use of a database which conducts a linear evaluation andcomparison of the tested signal with the signal values set forth in thedatabase as described below 27′, forming part of the signal processinglogic which determines the measured glucose concentration based on acomparison of tile measured and pre-processed transmission signal withpre-determined spectral data stored in the neural network 27. Oncecalculated, the glucose concentration is provided to the display 28mounted in the black box 30.

The conventional trained neural network 27, which is a standard backpropagation network with a single hidden layer, allows the device tolearn and discriminate between the target glucose substance from otherblood components. Likewise, the preferred embodiment using a database orlook-up table also contains target glucose values. In order to obtainthe ideal or target glucose values over the spectral range of 700 to1800 nm, tests were conducted on glucose dissolved in simulated blood.The simulated blood was i solution of 14.5% bovine hemoglobin and 5%albumin with synthetic noise in distilled water. These are the typicalconcentrations of hemoglobin and albumin found in human blood. The idealspectra values were measured using a VIS/NIR spectrometer. The measuredspectra were of simulated blood containing glucose concentrations in therange of 50 mg/dl to 600 mg/dl. Also, an empty curette data set wastaken for reference, as sell as one albumin data set, one deionizedwater data set and seven hemoglobin data sets. An ideal measurement wastaken without noise considerations, and a noisy measurement was takenwhich included a 5% noise component. During training of the neuralnetwork, adjustments are made to internal coefficients or weights untilthe network can predict the target value associated with each input towithin a predetermined acceptable tolerance.

The preferred neural network or database would contain approximately30-40 sets of target transmittance data corresponding to 30-40 differentglucose levels. Set forth in Table 1 are the descriptions of the testsubstances:

TABLE 1 Concen- N.N. Training Training Test Test Description trationTarget Output Error Output Error Glucose 9% 0.4 0.40191 0.5% 0.4018 0.4%Glucose 18% 0.5 0.49055 1.9% 0.4882 2.4% Glucose 36% 0.6 0.60116 0.2%0.6014 0.2% Albumin 0.3 0.29828 0.6% 0.2939 2.0% Deionized 0.2 0.200580.3% 0.2005 0.2% Water Hemoglobin 0.7 0.69965 0.0% 0.6939 0.9%Hemoglobin 0.72 0.71972 0.0% 0.7159 0.6% Hemoglobin 0.8 0.80149 0.2%0.7870 1.6% Hemoglobin 0.82 0.81838 0.2% 0.8112 1.1% Hemoglobin 0.840.83949 0.1% 0.8357 0.5% Hemoglobin 0.86 0.86286 0.3% 0.8526 0.9%Hemoglobin 0.88 0.87260 0.8% 0.8596 2.3% Empty 0.1 0.09956 0.4% 0.10040.4%

The present device using the above-described components, including adatabase containing target transmission glucose values, is generallyoperated as follows. First, a self-check of the device is performed toconfirm operation of the signal sensor assembly 11, including the LED 12and associated receptor 14. Next, several calibration steps areperformed to initialize the device. One such step is setting theintensity of the LED 12. This is determined based on the LED intensityfactor. The LED intensity factor is measured based on the high and lowdata values measured from the pulse waveform signal taken from the pulseof the subject. The pulse of the subject may be taken on one of the LED12 and associated receptors 14. Alternately, the pulse may be takenusing any number of conventional methods, the results of which arecollected and provided to the computer system 20. In the preferredembodiment, the high and low pulse data values are collected and used toobtain the pulse waveform signal which is converted from analog todigital and stored in the computer system 20 within the LED signalprocessor 40.

In both the neural network embodiment and the linear evaluationembodiment of the present device, an intensity factor is nextestablished using the pulse waveform signal. During initialization ofthe device, current is increasingly and incrementally supplied to an LED12 to increase the intensity of the light source. During collection ofthe signals the system offset point is increased to obtain approximately0.2 volts, and the system gain point is increased to obtainapproximately 6 volts. This stepped process is performed until aminimally distorted predetermined desirable signal is received by theassociated receptor 14. Once an acceptable signal is received, the thereoperating level of LED intensity is stored by the LED signal processor40, and becomes the current applied to the LED 12 during regularoperation of the device. A baseline voltage for the signal sensorassembly 11, 11′, 11″ is also preferably used in both embodiments. Thebaseline voltage used is within a range of 1.2-2.3 volts. The baselinevoltage is manually established by the user of the device. A generalizedselection of the type of body part being tested is made by the user,based on the “thin,”“average” or “heavy” nature of the subject. A seriesof buttons 170, or other manual selection device, is provided on thehousing 30 which enables the setting of a system voltage settingaccording to the body type selected. The thin setting establishes thebaseline voltage at approximately 1.2 volts. The average settingestablishes the baseline voltage at approximately 1.5 volts, and theheaving setting establishes the baseline voltage at approximately 2volts. In each of the embodiments, continuous checking of the LED andreceptor are performed to ensure proper operation of the device ismaintained at all times. A warning notice is provided to the operator intile event improper operation is detected.

Next in the calibration process, the device calculates when measurementsor readings should be taken by the device. Measurements of the LEDsignals are preferably only taken at a midpoint in the subject's bloodflow cycle. This has been previously described as the positive“baseline” of the pulse waveform signal, which, in the present device,means the positive difference between the high and low data values fromthe pulse waveform signal. As these signals are stored within theLED/sensor blocks 58 within the signal processor 40, timing of theoperation of the LEDs 12 is readily determined using the drive circuit60 as indicated in FIGS. 7-10.

Once these initial operations are completed, the signal sensor assembly11 is then operated at the times and increments calculated by and storedin the computer system 20, in particular the LED drive 60 and sequencercircuit 50, to measure each of the LED signals, all as indicated inFIGS. 7-10.

Measurements from each of the LEDs are taken several predetermined timesat each of the high and low pulsatile values measured over 5milliseconds, with the resulting sensor signal values amplified asdescribed, where in the LED signal processor 40. In the neural networkembodiment, the converted signals are averaged together to obtain asingle digital data value for each of the LED signals.

The final signal value is then converted in the analog-to-digitalconverter 42. The pre-processed digital signal from the LED signalprocessor 40 is then provided to the signal processing logic 26 withinthe P/C interface 46 of the computer system 20 via the I/O bus 49 asillustrated in FIG. 6. The trained neural network 27 supported on theP/C interface compares the glucose transmittance data provided via theLED signal processor 40 with the predetermined or target spectralglucose transmittance data stored within the neural network, and uponfinding a comparative value determines the glucose level of the subjectfrom the digital signal provided.

In the linear evaluation embodiment 27′ of the device, the high and lowsignal values stored are then normalized using computer software tofinally adjust the signal values. A continuous comparison of thenormalized transmission data or values is conducted to obtain thehighest and lowest transmission values collected. To further improve thesignal to noise ratio, the lowest value is then subtracted from thehighest values to obtain a single calculated transmission value. Thissingle calculated transmission value is then compared to the target dataor the predetermined glucose values stored within the database or lookuptable of the type used in the neural network embodiment, and previouslydescribed.

Upon successful comparison of the calculated transmission value with anequivalent target data value, by repeated comparisons between thecalculated and target values, the equivalent selected glucose level isthen provided to the digital display 28. Where the identical equivalentvalue is not found within the database, the next nearest points arelocated and a value is found by linear interpolation between the nextnearest points. In the event additional operations of the device on thesame subject are desired, tic subject preferably removes the sensorassembly, briefly massages the body part to ensure good blood flow,reattaches the assembly and manually selects the “test” button providedon the housing 30 to run another test. The device then repeats theentire process previously described, including initialization, since thesupport pieces of the assembly were moved, or some other problem mayhave occurred.

The preferred form of the glucose measuring apparatus 10 has beendescribed above. However, with the present disclosure in mind it isbelieved that obvious alterations to the preferred embodiment, toachieve comparable features and advantages in other assemblies, willbecome apparent to those of ordinary skill in the art.

We claim:
 1. A glucose measuring device for determining theconcentration of glucose in fluid within a body part of a subject,comprising: a) at least one light source emitting near infrared orinfrared light having a wavelength of between 640 and 1000 nm toilluminate the fluid, and at least one receptor associated with andopposite from said light source for receiving light emitted by saidlight source and transmitted through the fluid and body part of thesubject and generating a transmission signal representing the lighttransmitted from said first light source; b) a support piece having afirst plate for supporting said light source, and a second plate movablewith respect to said first plate for supporting said receptor associatedwith said light source; c) said support piece adapted to place a bodypart of a subject intermediate said first and second plates and toilluminate the body part and fluid using said light source; and d) asignal analyzer interconnected with said receptor for receiving saidtransmission signal and for determining from the transmission signal theglucose concentration in the fluid within the illuminated body part. 2.The device of claim 1, wherein said light source has a wavelength of 940nm.
 3. The device of claim 1 or 2, further including a second lightsource emitting near infrared or infrared light having a secondwavelength of either 650, 880, 940 or 1300 nm, which is different fromthe wavelength of said light source, to illuminate the fluid, and asecond receptor associated with said second light source for receivinglight emitted by said second light source and transmitted through thefluid and a body part of the subject and generating a secondtransmission signal representing the light transmitted from said secondlight source.
 4. The device of claim 3, wherein said second light sourcehas a wavelength of 880 nm.
 5. The device of claim 4, further includinga third light source emitting near infrared or infrared light having athird wavelength of either 650, 880, 940 or 1300 nm, which is differentfrom the wavelengths of said light source and second light source, toilluminate the fluid, and a third receptor associated with said thirdlight source for receiving light emitted by said third light source andtransmitted through the fluid and a body part of the subject andgenerating a third transmission signal representing the lighttransmitted from said third light source.
 6. The device of claim 5,wherein said third light source has a wavelength of 650 nm.
 7. Thedevice of claim 5, further including a fourth light source emitting nearinfrared or infrared light having a third wavelength of either 650, 880,940 or 1300 nm, which is different from the wavelengths of said lightsource, second and third light sources, to illuminate the fluid, and afourth receptor associated with said fourth light source for receivinglight emitted by said fourth light source and transmitted through thefluid and a body part of the subject and generating a fourthtransmission signal representing the light transmitted from said fourthlight source.
 8. The device of claim 7, wherein said fourth light sourcehas a wavelength of 1300 nm.
 9. The device of claim 7, further includinga second support piece having a first plate for supporting said thirdand fourth light sources, a second plate movable with respect to saidfirst plate for supporting said third and fourth receptors associatedwith their respective third and fourth light sources, and said secondsupport piece adapted to place a body part of a subject intermediatesaid first and second plates of said second support piece and toalternately illuminate the body part and fluid using said third andfourth sources.
 10. The device of claim 9, wherein said first and secondplates of said support piece are spring biased to provide contactingengagement of said light source supported on said first plate with oneside of the body part, and contacting engagement of said receptorsupported on said second plate with an opposite side of the body part.11. The device of claim 1, wherein said first and second plates of saidsupport piece are spring biased to provide contacting engagement of saidlight source supported on said first plate with one side of the bodypart, and contacting engagement of said receptor supported on saidsecond plate with an opposite side of the body part.
 12. The device ofclaim 1, further providing a display monitor interconnected with saidsignal analyzer for displaying the glucose concentration determined. 13.The device of claim 12, Wherein said signal analyzer is a trained backpropagation neural network with a single hidden layer.
 14. The device ofclaim 13, wherein the fluid measured within the body part isintravascular blood and the body part is the ear.
 15. A method fordetermining the glucose concentration in intravascular blood within abody part of a subject comprising the steps of: i) calibrating anon-invasive glucose measuring device by: a) measuring the pulsewaveform of a subject; b) incrementally increasing an electrical currentilluminating a first light source, incrementally reading a transmissionsignal generated in a corresponding first receptor associated with saidfirst light source, said first receptor positioned adjacent to andengaging the body part on an opposite side of the body part from saidfirst light source, and comparing incremental transmission signals untila predetermined desired quality of transmission signal is received fromsaid first light source; c) establishing said electrical current whichresulted in the desired quality of transmission signal as an operatingcurrent for illuminating said first light source during operation ofsaid glucose measuring device; ii) operating said non-invasive glucosemeasuring device at said operating current by: a) illuminatingintravascular blood within a body part using said first light sourcepositioned adjacent to and engaging the body part, said light sourcehaving a wavelength of between 640 to 1330 nm and being illuminated atsaid operating current; b) generating a transmission signal in saidfirst receptor from said first light source via the illuminatedintravascular blood of the body part, said first receptor positionedadjacent to and engaging the body part on an opposite side of the bodypart from said first light source; c) storing high and low values fromeach of the multiple transmission signals from the light source; d)selecting a highest value from the transmission signals generated toobtain a highest transmission value for said light source; e) selectinga lowest value from the transmission signals generated to obtain alowest transmission value for said light source; f) analyzing saidhighest and lowest transmission values to determine the glucoseconcentration in the intravascular blood within the body part; and g)displaying the glucose concentration.
 16. The method of claim 15,wherein the step of measuring the pulse waveform of a subject comprisesusing said first light source for measuring the pulse waveform.
 17. Themethod of claims 15 or 16, wherein the step of illuminatingintravascular blood within a body part using said first light sourcepositioned adjacent to and engaging the body part, uses a light sourcehaving a wavelength of 940 nm.
 18. The method of claim 17, furthercomprising the step of illuminating intravascular blood within a bodypart using a second light source positioned adjacent to and engaging thebody part and emitting near infrared or infrared light having a secondwavelength of either 650, 880, 940 or 1300 nm, which is different fromthe wavelength of said first light source, to illuminate the fluid, andgenerating a transmission signal in a second receptor, said secondreceptor associated with said second light source for receiving lightemitted by said second light source and transmitted through the fluidand body part of the subject, representing the light transmitted fromsaid second light source.
 19. The method of claim 18, wherein the stepof illuminating intravascular blood within a body part using said firstand second light sources is performed alternately, such that only onelight source is illuminated at any one time.
 20. The method of claim 19,further comprising the steps of selecting the highest and lowest valuesfrom the transmission signals generated to obtain a high and lowtransmission value from said second receptor, averaging the high and lowvalues from said transmission signals for said second light source,analyzing the averaged transmission signals to determine the glucoseconcentration in the intravascular blood within the body part, anddisplaying the glucose concentration.
 21. The method of claim 20,wherein the step of analyzing the highest and lowest transmission valuesby subtracting the lowest transmission value from the highesttransmission value and selecting a comparable value or interpolatingbetween the closest values from predetermined glucose transmissionvalues to determine the glucose concentration.
 22. The method of claim17, wherein the step of analyzing the highest and lowest transmissionvalues by subtracting the lowest transmission value from the highesttransmission value and selecting a comparable value or interpolatingbetween the closest values from predetermined glucose transmissionvalues to determine the glucose concentration.
 23. A glucose measuringdevice for determining the concentration of glucose in fluid within abody part of a subject, comprising: a) a light source consistingessentially of a single light source emitting near infrared or infraredlight having a wavelength of between 640 and 1330 nm to illuminate thefluid, b) at least one receptor associated with and opposite from saidlight source for receiving light emitted by said light source andtransmitted through the fluid and body part of the subject andgenerating a transmission signal representing the light transmitted; c)a support piece having a first plate for supporting said light source,and a second plate movable with respect to said first plate forsupporting said receptor associated with said light source; d) saidsupport piece adapted to place a body part of a subject intermediatesaid first and second plates and to illuminate the body part and fluidusing said light source; and e) a signal analyzer interconnected withsaid receptor for receiving said transmission signal and for determiningfrom the transmission signal the glucose concentration in the fluidwithin the illuminated body part.
 24. The device of claim 23, whereinsaid light source has a wavelength of approximately 940 nm.
 25. Thedevice of claim 23, wherein said first and second plates of said supportpiece are spring biased to provide contacting engagement of said lightsource supported on said first plate with one side of the body part, andcontacting engagement of said receptor supported on said second platewith an opposite side of the body part.
 26. The device of claim 24,wherein the fluid measured within the body part is intravascular bloodand the body part is the ear.
 27. The device of claim 23, furtherproviding a display monitor interconnected with said signal analyzer fordisplaying the glucose concentration determined.
 28. The device of claim27, wherein said signal analyzer is a trained back propagation neuralnetwork with a single hidden layer.